Nitroglycerin has long been recognized as a vasodilator having no significant toxic or other side effects. As a consequence, nitroglycerin has served extremely well in the treatment of angina pectoris. It has also been recognized that nitroglycerin is useful in treating such peripheral circulatory disorders as Raynaud's disease. Recent studies suggest that nitroglycerin ointment may be of value in treating patients having acute myocardinal infarction and congestive heart failure.
Nitroglycerin (glyceryl trinitrate) acts to relax vascular smooth muscle, thereby having a marked effect on the cardio-vascular system. In essence, the nitroglycerin decreases peripheral resistance to thereby produce a decrease in systolic blood pressure; it is also thought to dilate coronary blood vessels to thereby increase blood flow to the myocardium.
One of the disadvantages of nitroglycerin resides in the fact that in any form its effective life is very short. Once it reaches the portal circulation, it is rapidly cleared from the blood by the liver. Orally administered nitroglycerin is absorbed from the gastrointestinal tract and is degraded before it reaches the circulation system. Sublingually administered nitroglycerin is released directly into the circulatory system under the tongue, thereby avoiding destruction in the gastrointestinal tract and portal circulation.
The duration of nitroglycerin effect is related to the rate at which it can be absorbed into the circulation system. In sublingual administration, the vasodilating effects last 15 to 30 minutes. The development of nitroglycerin in ointment form has made it possible to sustain its effect for up to five hours. It is administration of the nitroglycerin in ointment form with which this invention is concerned.
Several factors influence percutaneous absorption of substances such as nitroglycerin ointment, primarily because the network of glands and vasculature in the skin is so complex. The stratum corneum, the outermost layer of the epidermis and principal barrier of the skin, plays an important role in absorption of substances applied to the skin. The passage of substances from the skin takes place primarily through hair follicles and sweat ducts in this skin layer. The main driving force through absorption of the skin is a concentration gradient. However, lipid material around and between the cells of the stratum corneum and within the openings of the apendages of the skin also play a major role in absorption. These lipids, along with water present in and around the cells, determine the kind of substances that will defuse easily across the skin. Increased hydration of the stratum corneum appears to expand the pores or channels in the skin and increases permeability of substances. Therefore, skin moisture affects the percutaneous absorption of nitroglycerin ointment.
While the application of nitroglycerin topically has become an accepted means of obtaining prolonged vasodilation, the actual measuring and applying the ointment has received scant attention. Conventionally, application of nitroglycerin ointment is performed by squeezing a prescribed dose of the ointment from a tube onto a dose measuring application paper. Typically, the dose is one to two inches in length, although some patients require higher dosages. The application paper is then applied, ointment side down, at any convenient, hairless sight on the patients body, usually the anterior chest. The application paper is then taped to the sight by suitable medical tape or the like. Finally, the sight is covered with plastic wrap which is taped to the patient's skin on all sides. Increases in skin temperature and hydration, which, in turn, enhances percutaneous absorption. This multi-step application process requires the nurse or other health care personnel to cut the plastic wrap and individual tape strips in advance and then hold the plastic wrap in position at each individual tape strip applied. This procedure, although seemingly simple in description, is awkward for the nurse and relatively time consuming.